Autoimmunity in New Zealand mice has a genetic and immune basis; however, expression of severity can be modified by viral and other environmental factors as well as sex hormones. The immunologic factors are complex. These include excessive B-cell activation and abnormal T cell function. The xid gene codes for the deletion of a B cell subset. This gene prevents disease in congenic NZB and (NZB x NZW)F mice. BXSB mice have a Y chromosome-linked gene which accelerates autoimmunity in autoimmune mice, but does not cause it in nonautoimmune mice. All of the autoimmue strains studied have a defect in experimental toleance. In NZB mice, the defect maps to a stem cell pre-T cell.